Growth Hormone-Releaser Diet Attenuates Cognitive Dysfunction in Klotho Mutant Mice via Insulin-Like Growth Factor-1 Receptor Activation in a Genetic Aging Model
Endocrinology and Metabolism
; : 336-348, 2014.
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| ID: wpr-44895
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ABSTRACT
BACKGROUND:
It has been recognized that a defect in klotho gene expression accelerates the degeneration of multiple age-sensitive traits. Accumulating evidence indicates that aging is associated with declines in cognitive function and the activity of growth hormone (GH)/insulin-like growth factor-1 (IGF-1).METHODS:
In this study, we examined whether a GH-releaser diet could be effective in protecting against cognitive impairment in klotho mutant mice.RESULTS:
The GH-releaser diet significantly induced the expression of IGF-1 and IGF-1 receptors in the hippocampus of klotho mutant mice. Klotho mutant mice showed significant memory impairments as compared with wild-type mice. In addition, the klotho mutation significantly decreased the expression of cell survival/antiapoptotic factors, including phospho-Akt (p-Akt)/phospho-glycogen synthase kinase3beta (p-GSK3beta), phospho-extracellular signal-related kinase (p-ERK), and Bcl-2, but significantly increased those of cell death/proapoptotic factors, such as phospho-c-jun N-terminal kinase (p-JNK), Bax, and cleaved caspase-3 in the hippocampus. Treatment with GH-releaser diet significantly attenuated both decreases in the expression of cell survival/antiapoptotic factors and increases in the expression of cell death/proapoptotic factors in the hippocampus of klotho mutant mice. In addition, klotho mutation-induced oxidative stress was significantly attenuated by the GH-releaser diet. Consequently, a GH-releaser diet significantly improved memory function in the klotho mutant mice. GH-releaser diet-mediated actions were significantly reversed by JB-1, an IGF-1 receptor antagonist.CONCLUSION:
The results suggest that a GH-releaser diet attenuates oxidative stress, proapoptotic changes and consequent dysfunction in klotho mutant mice by promoting IGF-1 expression and IGF-1 receptor activation.
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Phosphotransferases
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Vieillissement
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Facteur de croissance IGF-I
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Hormone de croissance
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Expression des gènes
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Récepteur IGF de type 1
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Stress oxydatif
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Régime alimentaire
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Caspase-3
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Hippocampe
Type d'étude:
Prognostic_studies
Limites du sujet:
Animals
langue:
En
Texte intégral:
Endocrinology and Metabolism
Année:
2014
Type:
Article